Nosyberkol is a Mycobacterium tuberculosis Small Molecule Macrophage Inhibitor

Iowa State University researchers and their collaborators have identified a compound that inhibits phagosomal maturation in macrophage cells of the mammalian immune system.

Suggested Uses

Starting point for pharmaceutical development; research tool for probing phagocytosis

Advantages

May serve as the basis for development of new antibiotics targeting edaxadiene biosynthesis

Innovation Details

Detailed Description

Mycobacterium tuberculosis is one of the most significant human pathogens known. It is estimated to infect nearly one third of the world’s population and causes nearly two million deaths each year. M. tuberculosis is an intracellular pathogen that is able to subvert normal phagosomal processing such that it is blocked at an early endosomal stage rather than maturing to a bactericidal phagolysosome. As part of an effort to investigate the mechanisms by which M. tuberculosis is able to prevent phagosome maturation, ISU researchers and their collaborators have identified nosyberkol (also known as isotuberculosinol and edaxadiene) as a novel M. tuberculosis diterpene virulence factor, which has been shown to arrest phagosome maturation in vitro. These researchers have also identified the enzyme that catalyzes the committed step in nosyberkol biosynthesis (halimadienyl diphosphate synthase; HPS) and identified potential HPS inhibitors. These findings have implications for new drug development as well as for probing the trafficking of intracellular pathogens and mechanisms involved in phagocytosis.

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